Journal Of The Peripheral Nervous System[JOURNAL]
Sun
200 papers
De Novo MFN2 p.Arg95Met in Severe Charcot-Marie-Tooth Disease Type 2A.
Lee HY, Cheng WL, Pan SH … +3 more , Lee CJ, Wei YH, Liu CS
J Peripher Nerv Syst · 2026 Sep · PMID 42338388 · Publisher ↗
BACKGROUND AND AIMS: Mitofusin 2 (MFN2)-related Charcot-Marie-Tooth disease type 2A (CMT2A) is often associated with early onset, severe progressive weakness, distal wasting, and reduced motor and sensory response amplit...
BACKGROUND AND AIMS: Mitofusin 2 (MFN2)-related Charcot-Marie-Tooth disease type 2A (CMT2A) is often associated with early onset, severe progressive weakness, distal wasting, and reduced motor and sensory response amplitudes. CASE REPORT: We report a 30-year-old Taiwanese woman with infancy-onset, severe axonal sensorimotor neuropathy, progressive distal weakness and wasting, optic atrophy, bilateral sensorineural hearing loss, hypophonia, and wheelchair dependence from adolescence. Nerve conduction study was consistent with severe chronic axonal sensorimotor polyneuropathy. Whole-exome sequencing identified a heterozygous de novo Mitofusin 2 (MFN2) variant, NM_014874.4:c.284G>T, predicting p.Arg95Met. INTERPRETATION: This case expands the genotypic spectrum of MFN2-related Charcot-Marie-Tooth disease type 2A and supports the clinical importance of the Arg94/Arg95 region in severe early-onset MFN2 neuropathy.
Autonomic Nervous System Phenotyping Across Chronic Demyelinating Peripheral Neuropathies: A Comparative Study.
Bjelica B, Todorovic T, Bozovic I … +4 more , Palibrk A, Jankovic V, Basta I, Peric S
J Peripher Nerv Syst · 2026 Jun · PMID 42321147 · Full text
BACKGROUND AND AIMS: This study aimed to systematically phenotype autonomic nervous system (ANS) involvement in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), monoclonal gammopathy of undetermine...
BACKGROUND AND AIMS: This study aimed to systematically phenotype autonomic nervous system (ANS) involvement in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), monoclonal gammopathy of undetermined significance-associated neuropathy (MGUS-PNP), Charcot-Marie-Tooth disease Type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP). METHODS: Autonomic symptoms were assessed using the SCales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT). Muscle strength and functional disability were evaluated using the Medical Research Council (MRC) scale, the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale, and the Overall Neuropathy Limitation Scale (ONLS). RESULTS: A total of 343 participants were included: 98 with CIDP (mean age: 59.2 ± 13.2 years), 51 with MGUS-PNP (66.0 ± 11.3 years), 51 with CMT1A (51.2 ± 13.1 years), 18 with HNPP (40.6 ± 15.1 years), and 125 healthy controls (58.2 ± 13.3 years). Compared with healthy controls, patients with CIDP, MGUS-PNP, and CMT1A showed significantly higher total SCOPA-AUT scores (p < 0.01). Distinct, disease-specific ANS symptom patterns were observed across neuropathy subtypes. Overall disability was independently associated with overall autonomic symptom burden in MGUS-PNP (β = 0.42, p < 0.05) and CMT1A (β = 0.68, p < 0.05). In CIDP, patients with active disease showed higher autonomic symptom burden than those with inactive disease (12.7 ± 11.7 vs. 8.6 ± 7.9, p = 0.042). INTERPRETATION: Patients with CIDP, MGUS-PNP, and CMT1A exhibit a substantial autonomic symptom burden with distinct disease-specific ANS patterns. These findings highlight the relevance of autonomic dysfunction in immune-mediated and hereditary neuropathies and warrant further studies to clarify their clinical and prognostic significance.
Circulating Inflammation-Related Proteins Linked to Corneal Neuroimmune Measures, Neuropathy Deficits, and Symptoms in Type 2 Diabetes.
Ponirakis G, Al-Janahi I, Elgassim E … +23 more , Dalloul RSD, Petropoulos IN, Gad H, Khan A, Zaghloul HB, Ali H, Siddique MA, Mohamed FFS, Ahmed LHM, Dakroury Y, El Shewehy AMM, Saeid R, Mahjoub F, Al-Noubi MN, Sarwath H, Paul P, Kaul R, Salivon I, Zirie MA, Al-Ansari Y, Atkin SL, Schmidt F, Malik RA
J Peripher Nerv Syst · 2026 Jun · PMID 42270126 · Publisher ↗
OBJECTIVE: Systemic inflammation plays a key role in diabetic peripheral neuropathy (DPN). This exploratory study investigated circulating inflammation-related proteins associated with corneal neuroimmune measures, neuro...
OBJECTIVE: Systemic inflammation plays a key role in diabetic peripheral neuropathy (DPN). This exploratory study investigated circulating inflammation-related proteins associated with corneal neuroimmune measures, neuropathic deficits, and symptoms in patients with type 2 diabetes (T2D). METHODS: Participants with T2D (n = 44) underwent assessment of corneal nerve morphology and dendritic cell density (DCD), vibration perception threshold (VPT), electrochemical skin conductance (ESC), DN4 questionnaire, and profiling of 92 plasma proteins using the Olink inflammation panel. RESULTS: A total of 30 proteins were associated with neuropathy deficits and corneal DCD. Corneal nerve measures showed positive associations with two chemokines, four epithelial-barrier cytokines, and two growth-related mediators, and negative associations with three inflammatory cytokines/receptors, one anti-inflammatory cytokine/receptor, two immune-regulatory molecules, and one chemokine. VPT was positively associated with three inflammatory cytokines/receptors, while ESC showed negative associations with one metabolic-inflammatory enzyme, one chemokine, and one inflammatory receptor. Neuropathic symptoms based on DN4 were positively associated with one immune-regulatory molecule and negatively with one neurotrophic factor and one homeostatic cytokine. Corneal DCD showed positive associations with four inflammatory cytokines and one neurotrophic factor, and a negative association with one epithelial chemokine. Non-branching DCD was negatively associated with corneal nerve branch density (p ≤ 0.05). CONCLUSIONS: Neuropathy deficits and corneal DCD in T2D are associated with distinct neuroimmune pathways.
A Quantitative Assessment of Upper Limb Motor Function Across Disease Stages in Hereditary Transthyretin Amyloidosis.
Hamedani M, Prada V, Massucco S … +23 more , Roveta E, Grandis M, Gemelli C, Schiavetti I, Signori A, Schenone C, Luigetti M, Guglielmino V, Sciarrone MA, Vitali F, Pradotto LG, Manganelli F, Tozza S, Palumbo G, Mazzeo A, Gentile L, Russo M, Luca M, D'Arma F, Pisciotta C, Fenu S, Pareyson D, Schenone A
J Peripher Nerv Syst · 2026 Jun · PMID 42246655 · Full text
BACKGROUND AND AIMS: Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic disease where early neuropathy signs are challenging to detect conventionally. This study aimed to evaluate hand motor performance in A...
BACKGROUND AND AIMS: Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic disease where early neuropathy signs are challenging to detect conventionally. This study aimed to evaluate hand motor performance in ATTRv using the Hand Test System (HTS) across disease stages and examine correlations with standard measures. METHODS: A total of 113 individuals were enrolled: 74 patients with ATTRv (divided according to Familial Amyloid Polyneuropathy [FAP] stage into FAP0: pre-symptomatic with confirmed TTR mutations, n = 16; FAP1: mild sensory/motor symptoms, n = 40; FAP2: ambulatory with assistance, n = 18) and 39 healthy controls. All participants underwent HTS evaluation; 9-Hole Peg Test (9HPT); handgrip and tripod pinch strength testing; Thumb Opposition Test (TOT); Neuropathy Impairment Score (NIS); Disabilities of the Arm, Shoulder and Hand questionnaire (DASH); and Quality of Life Diabetic Neuropathy (Norfolk QoL-DN) questionnaire. Group differences were analyzed with analysis of covariance and correlations with Pearson's coefficients. RESULTS: HTS parameters (Touch Duration, Inter-Tapping Interval, Movement Rate) significantly differed across stages between the FAP2 and all other groups, with some parameters distinguishing the FAP1 from the control and FAP0 groups. 9HPT impairment was observed only in the FAP2 group. Grip strength showed subtle changes, especially in the right hands of the FAP1 group, while tripod pinch strength declined during advanced stages. Several HTS parameters were correlated with NIS, DASH, Norfolk QoL-DN, and hand strength. Subclinical carpal tunnel syndrome possibly influenced early-stage results. INTERPRETATION: HTS detected stage-related motor differences in ATTRv and correlated them with standard measures, offering increased sensitivity to early neuropathic changes.
COQ7-Related Neuropathy: Two New Cases and Review of the Literature.
Theuriet J, Ribault S, Fontaine F … +11 more , Gueguen N, Jacquier A, Quadrio I, Dmitrievsky Z, Konyukh M, Bonneau D, Allouche S, Cassereau J, Verny C, Guillet-Pichon V, Pegat A
J Peripher Nerv Syst · 2026 Jun · PMID 42240099 · Publisher ↗
BACKGROUND AND AIMS: Biallelic variants in COQ7 have been associated with inherited neuropathy. COQ7 encodes a mitochondrial protein directly involved in coenzyme Q10 (CoQ10) biosynthesis. METHODS: Two unreported and unr...
BACKGROUND AND AIMS: Biallelic variants in COQ7 have been associated with inherited neuropathy. COQ7 encodes a mitochondrial protein directly involved in coenzyme Q10 (CoQ10) biosynthesis. METHODS: Two unreported and unrelated cases of COQ7-related neuropathy are presented, along with a review of all previously published cases to highlight the key clinical features. The frequency of COQ7 variants was assessed in our cohort of distal hereditary motor neuropathy (dHMN) patients with upper motor neuron (UMN) signs. RESULTS: The two patients were compound heterozygous for the COQ7 variants c.197T>A, p.(Ile66Asn) and c.478del, p.(Asp160Thrfs*11); the latter has not been reported. Symptoms began in childhood, and both were diagnosed with dHMN based on distal motor weakness predominantly affecting the lower limbs and a pure motor length-dependent axonal neuropathy on electrodiagnostic study. They had pes cavus and brisk reflexes. In the 28 patients identified in the literature, including the two reported herein, the median age at symptom onset was 10 years (IQR [5-11]). The predominant neuropathy subtype was dHMN (89%). Foot deformities were observed in 19/23 patients (83%). Signs of UMN involvement were present in 20/27 patients (74%). In fibroblasts, CoQ10 levels were low, and 6-demethoxy-CoQ10 (DMQ10) levels were elevated in all tested patients (8/8, 100%). No other case was identified in 71 patients with dHMN and UMN signs. INTERPRETATION: COQ7-related neuropathy is rare but should be considered in young patients presenting with distal hereditary motor neuropathy, especially when UMN signs are present. Elevated DMQ10 levels and low CoQ10 levels in fibroblasts represent valuable diagnostic biomarkers.
Health Equality and Socioeconomic Impact of Hereditary Sensory Neuropathy Type 1 (HSN1) in the UK.
Kramarz C, Recica L, Morrow J … +4 more , Skorupinska M, Rossor AM, Laurá M, Reilly MM
J Peripher Nerv Syst · 2026 Jun · PMID 42231561 · Publisher ↗
BACKGROUND AND AIMS: Hereditary Sensory Neuropathy Type 1 (HSN1) is a rare autosomal dominant neuropathy caused by variants in the SPTLC1 and SPTLC2 genes, resulting in sensory loss, motor weakness, chronic ulceration, a...
BACKGROUND AND AIMS: Hereditary Sensory Neuropathy Type 1 (HSN1) is a rare autosomal dominant neuropathy caused by variants in the SPTLC1 and SPTLC2 genes, resulting in sensory loss, motor weakness, chronic ulceration, and risk of limb amputation. Whilst the clinical manifestations are well characterised, the socioeconomic and psychosocial impact remains under-researched and poorly understood. This pilot study aimed to assess the health equality and socioeconomic impact of HSN1 on affected individuals in the UK. METHODS: A novel 28-item anonymised questionnaire focusing on employment, healthcare access, finance, mobility, and wellbeing was distributed to 50 genetically confirmed HSN1 patients from an UK cohort. Responses were collected electronically. Quantitative and qualitative data were analysed descriptively. RESULTS: A total of 37 participants (74%) responded. Of these, only 24% were in full-time work, with 24% taking early medical retirement. Nearly half (46%) felt the disease negatively impacted career progression. Although 49% requested workplace adjustments, responses were mixed, with some reporting inadequate or denied support. Healthcare access was inconsistent due to long wait times, restrictive referral criteria, and poor awareness of HSN1 outside specialist centres. Financial strain was common; 41% reported income loss, and 21% spent over £1000 annually on disease-related costs. Driving ability was affected in 48%, and over half reported reduced participation in social activities. Nearly half believed healthcare professionals lacked sufficient understanding of the disease. INTERPRETATION: HSN1 imposes a substantial burden beyond physical symptoms, affecting employment, finances, independence, and mental health. These results highlight the need for better patient-centred care and improved education for non-specialist healthcare professionals. This is particularly timely in the context of emerging disease-modifying therapies such as L-serine and future gene therapy trials. TRIAL REGISTRATION: SENSE trial NCT06113055.
Significance of Phrenic Nerve Conduction Study in the Electrodiagnosis of Guillain Barré Syndrome.
Tasdemir V, Sirin NG, Baslo SA … +8 more , Atakli D, Soysal A, Cakar A, Tekce HD, Parman Y, Baslo MB, Oge AE, Orhan EK
J Peripher Nerv Syst · 2026 Jun · PMID 42227702 · Publisher ↗
BACKGROUND AND AIMS: To determine the role of phrenic nerve conduction studies (NCS) in identifying subtypes of Guillain-Barré syndrome (GBS) and to investigate the correlations between phrenic NCS and clinical and respi...
BACKGROUND AND AIMS: To determine the role of phrenic nerve conduction studies (NCS) in identifying subtypes of Guillain-Barré syndrome (GBS) and to investigate the correlations between phrenic NCS and clinical and respiratory scores. METHODS: A clinical evaluation was conducted on 23 patients diagnosed with GBS, encompassing the Medical Research Council (MRC) sum scores, GBS disability scores, and Erasmus GBS Respiratory Insufficiency Scores (EGRIS). Electrodiagnostic studies (EDX) were conducted twice and bilateral phrenic NCSs once within the 6 weeks after symptom onset. The latency, peak-to-peak amplitude, and negative peak area of phrenic compound muscle action potential (CMAP) elicited using surface electrodes were measured, and the values indicating prolonged latency (≥ 110%-130% of upper limit of normal (ULN)) and/or prolonged negative peak duration (≥ 130% of ULN) were considered as demyelinating. RESULTS: Phrenic NCSs revealed 87.0% sensitivity and 89.5% specificity in the diagnosis of demyelinating subtype (cut-off value of latency 8.6 ms). Most of the phrenic CMAP parameters revealed moderate correlations with clinical scores and with the results of median and ulnar EDX studies. INTERPRETATION: Besides its importance for having correlations with clinical and respiratory features, phrenic NCS may improve the diagnostic sensitivity in differentiating GBS subtypes.
Associations Between Diabetes Distress, Diabetic Peripheral Neuropathy and Neuropathic Pain in People With Type 2 Diabetes-The Maastricht Study.
Cardon A, Cleal B, Due-Christensen M … +7 more , Dukers-Muijrers N, Kirketerp-Møller K, Rasmussen A, Ahluwalia TS, Hansen CS, Schram MT, Koster A
J Peripher Nerv Syst · 2026 Jun · PMID 42167749 · Publisher ↗
BACKGROUND AND AIMS: Diabetic peripheral neuropathy (DPN) and neuropathic pain are associated with various psychosocial factors, but the effect of diabetes distress remains underexplored. This study examines the associat...
BACKGROUND AND AIMS: Diabetic peripheral neuropathy (DPN) and neuropathic pain are associated with various psychosocial factors, but the effect of diabetes distress remains underexplored. This study examines the associations between diabetes distress, DPN, and neuropathic pain. METHODS: A cross-sectional analysis on participants with type 2 diabetes from The Maastricht Study was conducted. Diabetes distress was assessed with the PAID-20 questionnaire and categorized as low (score < 16), moderate (score 17-39), and high (score ≥ 40). Neuropathic pain was measured with the DN4 questionnaire, while DPN was clinically assessed through vibration perception threshold. Logistic regression analyses on the outcomes DPN only, neuropathic pain, and both DPN and pain were conducted, adjusted for sociodemographic (age, sex, education) and clinical characteristics (insulin use, HbA1c, depression). RESULTS: 1418 participants were included (median age: 64 years, 68.4% male). Moderate and high diabetes distress were observed in 22.5% and 4.8% of participants. Moderate (adjusted OR: 1.95; 95% CI: 1.37-2.75) and high distress (adjusted OR: 3.64; 95% CI: 1.97-6.63) were associated with the presence of neuropathic pain, but not with DPN alone. INTERPRETATION: Diabetes distress is strongly associated with neuropathic pain but not with DPN. These findings suggest that individuals with neuropathic pain may benefit from psychosocial screening and support.
A Novel Role of the Perineurium: Evidence for an Essential Function for Macrophage Maintenance and Increase in Isolated Peripheral Nerves.
Geldermann M, Klein D, Weiß EM … +1 more , Martini R
J Peripher Nerv Syst · 2026 Jun · PMID 42163496 · Publisher ↗
BACKGROUND AND AIMS: It is an established view that the perineurium surrounding peripheral nerves fulfills pivotal barrier functions to protect nerve fibers from noxious agents of the nerve environment. Here we want to i...
BACKGROUND AND AIMS: It is an established view that the perineurium surrounding peripheral nerves fulfills pivotal barrier functions to protect nerve fibers from noxious agents of the nerve environment. Here we want to investigate whether the perineurium also influences other endoneurial cells, like macrophages. METHODS: Peripheral nerve segments-either intact or deprived of their perineurium-were investigated in vitro for up to 9 days. Macrophages were quantified by immunohistochemistry using the pan-marker F4/80. Because elevated macrophage numbers can affect their proliferation and activation, we reduced their abundance in selected experiments by pretreating nerve donor mice with the CSF1-receptor inhibitor PLX5622. RESULTS: Endoneurial macrophage numbers in isolated nerve segments increased throughout the entire observation period. Removal of the perineurium caused a rapid and robust decline of macrophage numbers, reflecting its role on macrophage maintenance and expansion. Under these conditions, Schwann cells adopted an autophagic phenotype. When macrophages were pharmacologically reduced in number, they still preserved their capacity to expand in the normal nerve segments, with an initial preferential accumulation within the peripheral nerve region near the perineurium. Removal of the perineurium prior to culturing nerves with reduced macrophage numbers resulted again in a substantial loss of macrophages. INTERPRETATION: We identified a pivotal role of the perineurium in supporting macrophage maintenance and expansion. The perineurium may serve as a source of trophic factors and/or may form a barrier maintaining a critical concentration of trophic factors within the endoneurium. Additionally, macrophages may originate from a cell pool within the perineurium.
Clinical Diabetic Peripheral Neuropathy: Can It Be Reversed? Arguments for and Against From a NEUROdiab Debate.
Sloan G, Azmi S, Eid S … +7 more , Ferdousi M, Røikjer J, Kender Z, D'Onofrio L, Karlafti E, Callaghan B, Perkins BA
J Peripher Nerv Syst · 2026 Jun · PMID 42144696 · Full text
Diabetic peripheral neuropathy (DPN) is a prevalent and disabling complication of diabetes, yet whether established clinical DPN is reversible remains debated. At the 35th Annual Meeting of NEUROdiab, a formal debate exa...
Diabetic peripheral neuropathy (DPN) is a prevalent and disabling complication of diabetes, yet whether established clinical DPN is reversible remains debated. At the 35th Annual Meeting of NEUROdiab, a formal debate examined arguments 'for' and 'against' the proposition that clinical DPN can be reversed. This review summarises both perspectives and considers their implications for clinical practice and future research. Evidence supporting the reversibility of clinical DPN draws on four main observations. Therapies for hereditary transthyretin amyloidosis demonstrate that substantial improvement in a progressive length-dependent neuropathy is biologically achievable, providing a proof-of-concept in a different disease. Pancreatic transplantation in Type 1 diabetes leads to measurable improvements in large- and small-fibre indices. Structured lifestyle interventions and bariatric surgery improve intraepidermal nerve fibre density, suggesting that metabolic correction can promote neural repair. Finally, emerging agents such as topical oxybutynin show early promise in improving surrogate outcomes, reinforcing the argument that clinical DPN may be partially reversible. Arguments opposing reversibility emphasise that DPN resembles other microvascular complications, in which early abnormalities may regress but established clinical disease is not reversed. Heterogeneity in diagnostic thresholds, phenotype variability and inconsistent outcome measures complicates defining what constitutes true reversal. Long-term studies and major trials, including DCCT/EDIC and BARI 2D, demonstrate slowing of progression rather than restoration of normal nerve function. Moreover, numerous mechanistically promising agents have failed in human trials despite strong pre-clinical results. Collectively, these limitations support the view that established clinical neuropathy remains largely irreversible to date. Overall, the debate underscores that reversibility depends on timing, definitions and outcome thresholds. While early-stage dysfunction is more likely to be modifiable, complete restoration of established clinical DPN (such as full restoration of protective sensation) remains unproven. Future research should prioritise developing validated biomarkers and standardised endpoints in addition to searching for new therapeutics.
Application of a Clinical-Electrophysiological Model for Identifying Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Australian Cohort.
Swart G, Garg N, Skolka MP … +9 more , Yiannikas C, Vucic S, Pollard JD, Carroll AS, Silsby M, Spies J, Kiernan MC, Klein CJ, Park SB
J Peripher Nerv Syst · 2026 Jun · PMID 42117771 · Publisher ↗
Abstract loading — click title to view on PubMed.
Restless Legs Syndrome in Patients With PMP22-Related Neuropathies.
Bjelica B, Vujnic M, Vukojevic M … +5 more , Bozovic I, Andrejic N, Basta I, Rakocevic-Stojanovic V, Peric S
J Peripher Nerv Syst · 2026 Jun · PMID 42052752 · Full text
BACKGROUND AND AIMS: Restless legs syndrome (RLS) is frequently reported in peripheral neuropathies, but its prevalence and clinical correlates in Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy wit...
BACKGROUND AND AIMS: Restless legs syndrome (RLS) is frequently reported in peripheral neuropathies, but its prevalence and clinical correlates in Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) remain poorly defined. We aimed to determine RLS prevalence in CMT1A and HNPP and to assess associations with disease severity, muscle strength, disability, and quality of life (QoL). METHODS: Forty-seven CMT1A and 18 HNPP patients were included. RLS was diagnosed according to the International Restless Legs Syndrome Study Group criteria, and RLS severity was assessed with the International Restless Legs Syndrome Severity Scale (IRLS-SS). MRC Sum Score (MRC-SS), Charcot-Marie-Tooth Examination Score (CMTES), Overall Neuropathy Limitations Scale (ONLS), Beck Depression Inventory (BDI), Fatigue Severity Scale (FSS), and the 36-Item Short Form Health Survey (SF-36) were recorded. RESULTS: RLS was present in 29.8% of CMT1A and 38.9% of HNPP patients. CMT1A patients with RLS had longer disease duration (p = 0.05), worse muscle strength (p = 0.014), higher disease severity (p = 0.014), higher upper-limb (p = 0.005) and overall disability (p = 0.011), and higher fatigue severity (p = 0.011) compared with those without RLS. HNPP patients with RLS showed higher upper-limb (p = 0.034) and overall disability (p = 0.032), higher depression (p = 0.005), and fatigue severity (p = 0.018) than those without RLS. QoL was significantly impaired in patients with RLS in both groups, and RLS severity negatively correlated with physical and mental QoL domains. INTERPRETATION: RLS is common in CMT1A and HNPP and is associated with increased disease severity, greater functional disability, and reduced QoL. Clinicians should screen for RLS in PMP22-related neuropathies and consider symptomatic management.
Measurement of Red Blood Cell Sorbitol Dehydrogenase Activity for Fast Screening of SORD-Related Neuropathies.
Moro N, Francois S, Grondin C … +18 more , Ben Salem S, Rajagopal S, Aykut D, Arezki L, Larramendi JM, Berquet C, Willems M, Bouchet-Séraphin C, Gauthier LW, Konyukh M, Svahn J, Moutereau S, Peoc'h K, Tard C, Fernández-Eulate G, Stojkovic T, Bruneel A, Raynor A
J Peripher Nerv Syst · 2026 Jun · PMID 42021567 · Publisher ↗
BACKGROUND AND AIMS: To develop an assay to measure red blood cell (RBC) sorbitol dehydrogenase (SORD) activity for fast laboratory screening of SORD-related neuropathies, and to provide additional phenotypic arguments i...
BACKGROUND AND AIMS: To develop an assay to measure red blood cell (RBC) sorbitol dehydrogenase (SORD) activity for fast laboratory screening of SORD-related neuropathies, and to provide additional phenotypic arguments in case of ambiguous genetic results. METHODS: Hemolysates were incubated in the presence of fructose and NADH to produce sorbitol and NAD. The decrease in absorbance at λ = 340 nm was monitored throughout the course of the reaction. Results were expressed as % activity compared to a within-run control. A cohort of 38 individuals was evaluated over 13 runs: 13 individuals served as within-run controls, 3 were diagnosed with SORD deficiency, 2 were highly suspected of having SORD deficiency, 1 exhibited incidental genomic findings in the SORD gene, and 19 presented with neuropathy or myopathy of undetermined etiology. RESULTS: RBC SORD activity was significantly reduced in individuals diagnosed with SORD deficiency when compared to within-run controls, whereas in contrast, individuals without SORD deficiency did not exhibit this reduction. A comparison of these two groups showed that activities were significantly lower in deficient individuals (p = 0.00006). A test cutoff of < 30% yielded 100% sensitivity and specificity to detect deficient individuals. INTERPRETATION: This test provides a useful alternative to measuring plasma or urine sorbitol with mass spectrometry, allowing clinicians to directly evaluate SORD activity in RBC. As a result, it enables quick and convenient screening for SORD-related neuropathies during standard clinical procedures.
Biallelic Nonsense Variants in NEFL May Cause a Non-Length-Dependent Neuropathy With Temporal Dispersion on Nerve Conduction Studies.
da Silva Gomes MVV, Tomaselli PJ, Marques W
J Peripher Nerv Syst · 2026 Jun · PMID 41906391 · Full text
BACKGROUND AND AIMS: Pathogenic variants in NEFL, the gene that encodes the light polypeptide subunit of neurofilaments, are an uncommon cause of autosomal recessive Charcot-Marie-Tooth (CMT) disease. In this study, we d...
BACKGROUND AND AIMS: Pathogenic variants in NEFL, the gene that encodes the light polypeptide subunit of neurofilaments, are an uncommon cause of autosomal recessive Charcot-Marie-Tooth (CMT) disease. In this study, we describe the clinical and electrophysiological features of two families with early-onset CMT carrying nonsense variants in the NEFL gene. METHODS: Clinical, genetic, and electrophysiological data were collected prospectively and systematically analyzed. RESULTS: Five patients from two unrelated families were included. All patients had combined proximal and distal muscle weakness and facial weakness. In two individuals, marked proximal weakness of the upper limbs with preserved proximal strength in the lower limbs was observed, suggesting a non-length-dependent pattern of involvement. Pinprick sensation was preserved in all cases, whereas vibration sense was reduced, mainly distally. Nerve conduction studies demonstrated a demyelinating neuropathy with temporal dispersion in all patients. Whole-exome sequencing of the probands identified two distinct homozygous pathogenic nonsense variants in NEFL: c.54G>C; p.Tyr18* in proband I-1 and c.796G>T; p.Glu266* in proband II-1. Sanger sequencing confirmed segregation of the respective variants in affected siblings. INTERPRETATION: This study suggests that recessive nonsense variants in NEFL may cause a non-length-dependent sensory and motor neuropathy with facial involvement and temporal dispersion on nerve conduction studies, mimicking an acquired inflammatory demyelinating neuropathy.
A Next-Generation ELISA for the Detection of Anti-(Para)Nodal Antibodies in Autoimmune Nodopathy and COVID-19 Vaccinated Individuals.
Appeltshauser L, Ruprecht C, Reusch J … +7 more , Mees J, Glenewinkel H, Sommer C, Krone M, Wagenhäuser I, Doppler K, Petri N
J Peripher Nerv Syst · 2026 Jun · PMID 41906364 · Full text
BACKGROUND AND AIMS: Autoimmune nodopathy (AN) is a subtype of antibody-mediated inflammatory neuropathy targeting the node of Ranvier (NoR). Diagnosis requires detection of anti-(para)nodal autoantibodies like contactin...
BACKGROUND AND AIMS: Autoimmune nodopathy (AN) is a subtype of antibody-mediated inflammatory neuropathy targeting the node of Ranvier (NoR). Diagnosis requires detection of anti-(para)nodal autoantibodies like contactin-1 and neurofascin-155 via ELISA or cell-based assays, but protocols are inconsistent. Causes of node autoimmunity are unknown, and respiratory infections, including SARS-CoV-2 infection or COVID-19 vaccination as triggers, have not been thoroughly investigated. We aim to establish and validate a next-generation automated ELISA for anti-(para)nodal antibodies and investigate whether low-titer antibodies occur in recently COVID-19-vaccinated healthy individuals. METHODS: We used the Ella platform to customize an automated ELISA for anti-contactin-1, -neurofascin-155, and -Caspr-1 serum IgG. Patients with known AN (23 anti-neurofascin, 13 anti-contactin-1, and 8 anti-Caspr-1), 64 patients with seronegative (sub) acute inflammatory neuropathies, and 30 healthy controls served for validation, including quality analysis versus standard ELISA. Thirty-seven diagnostic samples of patients with suspected AN and 280 sera of healthcare workers included in the CoVacSer study, collected 3 weeks after COVID-19 vaccination or infection, were tested for anti-contactin-1 and anti-neurofascin-155. RESULTS: The automated ELISA showed high sensitivity (87.5%-100%) and specificity (98.4%-100%) for identifying AN, with reduced hands-on time, high automation, and similar quality and titer characteristics as standard ELISA. Low-titer anti-neurofascin-155, but no anti-contactin-1 autoantibodies, were detected in 1/280 post-SARS-CoV-2-vaccination or infection sera (0.36%). Longitudinal testing and clinical assessment did not indicate SARS-CoV-2-related neurological symptoms. INTERPRETATION: We provide a highly automated, rapid, universally applicable test platform for anti-(para)nodal antibodies. The low frequency of anti-(para)nodal antibodies and absence of clinical AN manifestations in COVID-19-vaccinated individuals support vaccination safety regarding AN development.
SOX5 Overexpression in Schwann Cell Combined With Chitosan-Based Conduit Promotes Peripheral Nerve Regeneration.
Ma B, Zhang F, Su J … +4 more , Gu B, Duan L, Zhang W, Kou Y
J Peripher Nerv Syst · 2026 Mar · PMID 41873109 · Publisher ↗
BACKGROUND AND AIMS: Severe peripheral nerve injury (PNI) remains a major clinical challenge, and functional recovery after conventional neurorrhaphy is often unsatisfactory due to fascicular mismatch, suture tension, an...
BACKGROUND AND AIMS: Severe peripheral nerve injury (PNI) remains a major clinical challenge, and functional recovery after conventional neurorrhaphy is often unsatisfactory due to fascicular mismatch, suture tension, and limited Schwann cell viability. To address these limitations, we previously developed a small-gap chitosan-based conduit that provides a controlled microenvironment for regenerative interventions. This study aimed to investigate whether SOX5 overexpression enhances Schwann cell regenerative potential and, when combined with this conduit, synergistically promotes peripheral nerve regeneration. METHODS: Schwann cells were transduced with SOX5 lentivirus and assessed for proliferation, migration, and neurotrophic factor secretion in vitro. In a rat sciatic nerve transection model (2-mm gap), animals received a chitosan conduit with intraluminal injection of SOX5 lentivirus. Histological, electrophysiological, and behavioral assessments were conducted at 12 weeks post-surgery. RESULTS: SOX5 overexpression significantly enhanced Schwann cell proliferation, migration, and secretion of BDNF, NGF, CNTF, and VEGF, while maintaining the dedifferentiated repair phenotype. In vivo, the combination of SOX5 lentivirus and chitosan conduit improved axonal regeneration, reduced muscle atrophy, and increased conduction velocity and locomotor recovery relative to the empty conduit group. INTERPRETATION: Lentivirus-mediated SOX5 overexpression drives Schwann cells toward a repair phenotype and, when integrated with a small-gap chitosan-based conduit, effectively promotes structural and functional nerve regeneration.
A New Simple SCreening Tool for Painful Diabetic Neuropathy (ACT) in Ecuador.
Gad H, Moreno MC, Pluas A … +8 more , Tello MB, Burgos M, Diaz K, Icaza E, Sanchez M, Vecchionacce M, Malik RA, Solis C
J Peripher Nerv Syst · 2026 Mar · PMID 41850574 · Full text
BACKGROUND: Diabetic painful neuropathy is a cause of significant disability and sleep disturbance but may be undiagnosed in up to 80% of patients with diabetes. Various neuropathic pain (NP) questionnaires have good dia...
BACKGROUND: Diabetic painful neuropathy is a cause of significant disability and sleep disturbance but may be undiagnosed in up to 80% of patients with diabetes. Various neuropathic pain (NP) questionnaires have good diagnostic utility but are impractical in resource-constrained and busy clinical settings. A simple sCreening Tool (ACT) was developed as a concise, patient-led tool to rapidly detect NP. This study evaluates the screening validity and psychometric properties of ACT compared with the DN4 questionnaire (reference standard). METHODS: We conducted an observational study employing clinic-based recruitment of patients with diabetes at a tertiary outpatient clinic in Guayaquil, Ecuador. All enrolled participants completed the ACT, DN4, and MNSI questionnaires during the study visit. MNSI was administered as part of the study to confirm the diagnosis of DPN using predefined cut-offs (MNSI-q ≥ 4 and MNSI-e ≥ 2.5). Time to completion, inter-item consistency, sensitivity, specificity, Youden's index, and the area under the receiver operating characteristic (ROC) curve were calculated for ACT using DN4 ≥ 4 as the criterion for NP. RESULTS: Of the 300 participants (median age 63 years, diabetes duration 10 years), 65 (21.7%) had NP per DN4. Total ACTq+e (questionnaire+examination) yielded a cut-off score of ≥ 6 items as optimal, with area under the ROC curve 0.836, sensitivity 80.0% and specificity 75.7% for painful DPN. ACT demonstrated moderate internal consistency (Cronbach's alpha = 0.65) and was well received by patients and clinicians on face validity. The completion time for ACT was comparable to that of DN4. CONCLUSION: The ACT tool is a rapid screening tool for identifying neuropathic pain in the busy clinic, with acceptable sensitivity and specificity compared to DN4. The brevity and ease of patient self-administration of ACT make it promising for integration into busy outpatient workflows to improve the diagnosis of painful DPN.
Motor Neuronopathy With Widespread Fasciculations in MCM3AP-Related Disorder: Clinical and Muscle MRI Insights.
Lemos AFA, Frezatti RSS, Dos Santos AC … +2 more , Tomaselli PJ, Marques W
J Peripher Nerv Syst · 2026 Mar · PMID 41819534 · Full text
BACKGROUND: Biallelic pathogenic variants in MCM3AP, encoding the germinal center-associated nuclear protein (GANP), have been linked to autosomal recessive peripheral neuropathies variably accompanied by cognitive impai...
BACKGROUND: Biallelic pathogenic variants in MCM3AP, encoding the germinal center-associated nuclear protein (GANP), have been linked to autosomal recessive peripheral neuropathies variably accompanied by cognitive impairment and multisystem involvement. To date, anterior horn cell involvement has not been documented in association with MCM3AP-related disorders. OBJECTIVE: To describe a patient with biallelic MCM3AP variants presenting with a motor neuronopathy phenotype and to provide the first whole-body muscle MRI characterization associated with this gene. METHODS AND RESULTS: A 53-year-old woman born to non-consanguineous parents presented with early-onset motor neuronopathy and lifelong learning difficulties. Neurological examination revealed generalized areflexia and widespread fasciculations without sensory abnormalities. Electroneuromyography demonstrated diffuse mixed acute-on-chronic denervation process. Whole-body muscle MRI showed a selective non-length-dependent pattern of fatty infiltration. Whole-exome sequencing identified two likely pathogenic heterozygous variants in the MCM3AP gene. STANDARD PROTOCOL APPROVALS, REGISTRATIONS, AND PATIENT CONSENTS: According to the policies of our institution, single-patient case reports do not require review or approval by the institutional ethics committee. Written informed consent for participation and for publication of clinical information, photographs, electrophysiological data, and muscle MRI images was obtained from the patient. No clinical trial registration was applicable. CONCLUSION: This case extends the phenotypic spectrum of MCM3AP-related disorders to include a slowly progressive, non-syndromic motor neuronopathy with electrophysiological evidence of active denervation and distinctive MRI findings. These observations highlight the hidden boundaries between hereditary motor neuropathies and anterior horn cell diseases, emphasizing the need for integrated clinical, neurophysiological, and genetic evaluation.
CIDP With and Without Monoclonal Gammopathy of Undetermined Significance (MGUS): Comparison of Clinical Phenotype, Diagnostic Features, and Treatment Response.
van Veen R, Baars AE, van Doorn IN … +14 more , Michael M, Bus SRM, Broers MC, van der Pol WL, Van Doorn PA, Drenthen J, Verhamme C, Vos JMI, van Schaik IN, Goedee HS, Wieske L, Jacobs BC, Eftimov F, ICOS Consortium
J Peripher Nerv Syst · 2026 Mar · PMID 41819123 · Full text
BACKGROUND AND AIMS: Monoclonal gammopathy of undetermined significance (MGUS) occurs in some patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but its impact on clinical phenotype and treatment res...
BACKGROUND AND AIMS: Monoclonal gammopathy of undetermined significance (MGUS) occurs in some patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but its impact on clinical phenotype and treatment response remains unclear. We assessed the prevalence of paraproteinemia in CIDP and compared disease features between CIDP patients with and without MGUS. METHODS: We used data from the International CIDP Outcome Study (ICOS), a prospective cohort study. We compared the prevalence and causes of paraproteinemia in CIDP to matched disease controls (axonal polyneuropathy or motor neuron disease) and compared disease features and treatment responses between CIDP patients with and without MGUS. Treatment response, defined as a ≥ 1-point improvement on the modified Rankin scale, was retrospectively assessed. RESULTS: IgG paraproteinemia was more common in CIDP than in controls (9%, 17/193 vs. 3%, 6/192; p = 0.03). IgM and IgA paraprotein prevalences did not differ. One CIDP patient had Waldenström macroglobulinemia; others had MGUS. Patients with IgG MGUS less often had an acute clinical presentation (6% vs. 33%; p = 0.02), more often had sensory deficits (94% vs. 67%; p = 0.02), and prolonged distal CMAP duration (64% vs. 31%; p = 0.02), compared to patients without MGUS. First-line treatment response rates were comparable (80% [IgG MGUS] vs. 67% [no MGUS]; p = 0.39). INTERPRETATION: IgG MGUS is more prevalent in CIDP than in controls. Presence of IgG MGUS is weakly associated with some CIDP disease features, but not treatment response. These findings indicate that, although IgG MGUS is associated with CIDP, the presence of IgG MGUS does not constitute a distinct subgroup with unique clinical features or treatment implications.
Overall Diagnostic Performance of Multiple Versus Single Physical Examination Tests for the Prediction of Future Diabetic Neuropathy Risk.
Parikh E, Al Mulla A, Lovblom LE … +6 more , Budhram DR, Orszag A, Falappa M, Gad H, Bril V, Perkins BA
J Peripher Nerv Syst · 2026 Mar · PMID 41802842 · Publisher ↗
BACKGROUND: The American Diabetes Association recommends three rather than one physical examination test for diabetic peripheral neuropathy (DPN) screening, although supporting evidence for the more complex screening str...
BACKGROUND: The American Diabetes Association recommends three rather than one physical examination test for diabetic peripheral neuropathy (DPN) screening, although supporting evidence for the more complex screening strategy remains limited. AIMS: We aimed to determine if a three-test strategy was superior to a single-test in sensitively identifying early stages of neuropathy risk. METHODS: Using longitudinal data from 170 adults without DPN, we compared the overall accuracy, represented by the area under the receiver operating characteristic curve (AUC), for the three-test versus one-test strategies. These were conducted for monofilament, pinprick, and vibration sensation compared to the Sum of Abnormal Tests (primary analysis) or a model-based probability from quantitative scores for each test in the prediction of nerve conduction study-defined incident DPN. RESULTS: Incident DPN occurred in 53 (31%) participants over a mean 4-year follow-up. Predictive AUC for both the Sum of Abnormal Tests or the model-based probability did not differ from the AUC for monofilament (0.66 vs. 0.71, p = 0.05 and 0.71 vs. 0.71, p = 0.79, respectively). INTERPRETATION: A complex three-test strategy did not outperform the best-performing single-test strategy, implying that practice guidelines that recommend simplified approaches to neuropathy screening are valid.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe